Overeating and obesity are significant health problems for Americans of all ages. The proposed studies will examine, in mice of normal and obese genetic backgrounds, the effects of imposing economic costs (lever presses) on food intake and patterns of eating. Additionally, we will examine whether prospective appetite suppressant drugs become more effective under conditions of selectively imposed economic costs. Both human and animal models point to multiple causes of obesity, including genetic predispositions to gain weight, ready availability of highly caloric foods, and reduced everyday exercise. Animal models have been instrumental in understanding genetic abnormalities that produce obesity but these models have been tested almost exclusively in environments in which there is no cost associated with obtaining food. In contrast, the evolution of abilities to procure and utilize food in hard times has been critical. It is important to develop and test animal protocols in which the effect of effort on food procurement and consumption are measured, and also to assess the effect of potential treatments in these protocols. Specifically, the protocols that we will use are "closed economy" in which mice must obtain all of their food in that environment. The first aim is to examine in outbred ICR:CD1 mice whether several types of economic cost, simulated by lever pressing as a fixed price (ratio), as a premeal foraging or procurement cost, or as an incrementing cost during the meal (progressive ratio) affect meal patterns. The latter two types of cost are predicted to have opposite effects on meal parameters, so we will also test their combination and develop a brief or streamlined protocol for future testing. The second aim, using the streamlined closed economy protocol, is to test whether mice either heterozygous or homozygous for genetic deletion of melanocortin 4 receptor deletion exhibit altered meal patterns or elasticity of food demand compared with wild type controls. The third aim, again using the streamlined protocol and outbred CD1 mice, is to examine whether chronic treatment with putative anorectic agents affect economic food choices. The agents to be studied are serotonergic agonist dexfenfluramine and the cannabinoid receptor antagonist rimonabant. The proposed studies will be the first to address the issue of behavioral change induced by anorectics under such conditions of simulated economic costs. [unreadable] [unreadable] [unreadable]